Standard versus High Intensity CXL after Thermal Keratoplasty

1. Standard versus High Intensity CXL after Thermal Keratoplasty Arthur Cummings Wellington Eye Clinic, Dublin, Ireland UPMC Beacon Hospital, Dublin, Ireland

2. Literature

3. International CXL Meeting • Why do we wait for evidence of progression to treat KC, especially in young patients? • Combination procedures more common

4. Combination Treatments • Topography-Guided PRK • Intacs • Keraflex

5. Keraflex and Cross-Linking for the Treatment of Keratoconus

6. Background • Corneal Collagen Cross-Linking (CXL) has been around for more than 10 years now • CE approved 2007 • Very successful at • Slowing down progression of keratoconus (KC) • Stabilizing and preventing progression of KC • Improving the corneal topography in some cases • When this improvement does occur, it is typically very modest (approx. 2.1 D of corneal flattening)

7. Background • We regard success as any halting of the progression of KC • But, how successful is it if the corneal shape is still distorted? • Techniques exist today for first improving the corneal shape (topography) and then “locking” these improved shapes in with CXL • SimLC (Simultaneous topography-guided PRK + CXL) • Intacs followed by CXL (as needed) • Thermal remodelling (Keraflex) with simultaneous or sequential CXL

8. Background • The concern with any thermal procedure is stability • The question is: Will CXL stabilize the cornea and reduce the regression of the flattening induced by Keraflex? • Keraflex effect would regress completely within 3 months if NO CXL was performed

9. Methods • 4 KC eyes underwent Keraflex and sequential CXL 4 to 7 days later in October 2010 • 4 KC eyes underwent Keraflex and simultaneous KXL* in March 2011 • 6 KC Eyes underwent Keraflex with sequential KXL* 5-6 hours later in September 2011 *KXL = Accelerated CXL (3 min. illum. (from Avedro))

10. Methods: Keraflex procedure • Vedera System delivers a single low energy microwave pulse lasting only a few milliseconds • Energy is applied using a dielectrically shielded microwave emitter • Non-invasively contacts the epithelial surface • The single pulse raises the temperature of the 4.0mm ring of corneal stroma to approximately 65°C • The collagen shrinks and forms a toroidal lesion in the upper 150 microns of the stroma below Bowman’s membrane

11. Methods Day 5 Post-op appearance with bandage CL in situ Microwave handpiece, positioned and engaged Applicator ring centered over corneal apex

12. Immediate Flattening from Keraflex Pre-Keraflex Post-Keraflex Difference Map 29 dioptres of flattening 15 dioptres of flattening 14 dioptres of flattening 30 dioptres of flattening

13. Results: 1st 4 Eyes - Sequential CXL 3mW for 30 minutes CXL 20 minute plus pre-soak Pre-treatment Patient 1 Patient 2 Patient 3 Patient 4 6 Months Post Keraflex + CXL

14. Sequential CXL: K-Max

15. Sequential CXL: Average K

16. Results: 1st 4 Eyes - Simultaneous KXL 30mW for 3 minutes KXL 8-10 minute pre-soak Pre-treatment Patient 1 Patient 3 Patient 4 Patient 2 3 Month Post Keraflex + KXL

17. Simultaneous KXL: K-Max

18. Simultaneous KXL: Average K

19. Summary • 3 month data showed that simultaneous Keraflex / KXL failed • Meanwhile, sequential CXL 5 days later was still doing well at 6 months and even 12 months for eyes with follow-up

20. Summary of Keraflex timeline 1 Week 1 Month 3 Months 6 Months Keraflex Keraflex with CXL 4 – 7 days later Keraflex with simultaneous CXL Keraflex with CXL 1 hour later

21. Hypothesis of Effect • There will be a rebound effect where cornea steepens directly after Keraflex • This effect is stronger than the CXL effect • If CXL is applied once the rebound effect has slowed / weakened, it may be able to hold the Keraflex effect long term • The earlier CXL is applied, the flatter the final shape

22. Keraflex list of 15 September 2011 1 Hour 2 Hours 3 Hours 6 Hours Keraflex CXL

23. Keraflex: Tracking the Corneal Rebound with Scheimpflug Imaging • 6 Eyes treated with Keraflex and sequential KXL 4 to 5 hours later on the same day • Treated >2 months ago

24. Keraflex: Tracking the Corneal Rebound with Scheimpflug Imaging Biggest rebound K-Max

25. Keraflex: tracking the corneal rebound with Scheimpflug imaging K-Avg Biggest rebound

26. Results: Last 6 Eyes - Sequential(6 hours later) KXL 30mW for 3 minutes KXL 20 minute pre-soak 30mW for 3 minutes KXL 20 minute plus pre-soak Pre-treatment Patient 1 Patient 3 Patient 4 Patient 5 Patient 6 Patient 2 1 Month Post Keraflex + KXL

27. K-Max timeline Sequential KXL 6 hours later Immediate 3 Months 2 hours 6 hours 1 Day 6 Weeks 1 hour 4 hours 5 Days Pre-op

28. K-Avg timeline Sequential KXL 6 hours later Immediate 3 Months 2 hours 6 hours 1 Day 6 Weeks 1 hour 4 hours 5 Days Pre-op

29. Variables • 1) Timing: • Sequential: Hours versus Days • Simultaneous • 2) Intensity • 3mW versus 30mW • 3) Soak time • 20 minutes plus versus 8-10 minutes

30. Study • Not designed to differentiate these factors • Clinical impression is that the most important factors are: • Timing • Soak time • Intensity of UV-Light

31. What I have learned • Next Keraflex list: • Keraflex • Cross-linking either same or next day • 20 minute Riboflavin soak • Possibly wait even a week until ideal or best possible shape has been achieved

32. Thank You for Your Attention